In this resubmission, originally in response to PA-96-048, "Expanded Research on Emerging Diseases," we propose to characterize the epidemiology of endemic cryptosporidiosis (C. parvum, CP) in Massachusetts. CP kills immunocompromised people. No consistently effective treatment exists. It causes waterborne epidemics, and likely leads to economically important minor illness in the general population. Modern surveillance tools for this infection are lacking. US water authorities are faced with the potential need to further protecting drinking water (at a cost of billions of dollars) with highly inadequate information. We hypothesize that highly integrated, simultaneously used detection tools, including several novel ones, will allow better estimation of the C. parvum disease burden, and lead to rational prevention strategies. We further hypothesize that this approach may prove useful in evaluating other emerging diseases, such as those caused by the caliciviruses, Microsporidia, and Cyclspora. We will test these hypotheses by monitoring C. parvum and its surrogates in 3 MA water supplies, including the major one for Boston. These measures and other environmental data will be linked to subsequent exposure, infection, and disease in a prospectively followed pediatric cohort that lives in cities served by these 3 water supplies, and in the general MA population. We will closely monitor a variety of immunological markers, including antibodies to oocyst and tissue stage antigens evaluating systemic, mucosal, and cellular responses, in both our cohort and in the general population, comparing a variety of potential surveillance tools. In addition, in exploratory efforts to validate these methods, we will use cutting-edge methods to survey these water supplies for Microsporidia, and genetically compare oocysts from children with disease to oocysts captured from our monitored water supplies. The statistical methods developed by our group are uniquely suited to this form of analysis. Our specific aims are: SA1: Prospectively follow a pediatric cohort to describe the relationships between clinical disease, exposure, and immunological markers. SA2: Estimate rates of exposure and infection in the general pediatric population, using anonymously retested Pb screening samples and serological techniques; SA3: Link waterborne CP to disease in the cohort (1), in the general pediatric population (2), and to gastroenteritis in the general population using HMO data; SA4: explore the utility of these methods for other pathogens, such as Microsporidia.